AU636835B2 - Device for release of substances, process for its manufacture and use thereof - Google Patents

Device for release of substances, process for its manufacture and use thereof Download PDF

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AU636835B2
AU636835B2 AU22506/88A AU2250688A AU636835B2 AU 636835 B2 AU636835 B2 AU 636835B2 AU 22506/88 A AU22506/88 A AU 22506/88A AU 2250688 A AU2250688 A AU 2250688A AU 636835 B2 AU636835 B2 AU 636835B2
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weight
pressure sensitive
substances
sensitive adhesive
substance
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AU2250688A (en
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Hans-Rainer Hoffmann
Halvor Jaeger
Robert-Peter Klein
Reinhold Meconi
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LTS Lohmann Therapie Systeme AG
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/58Adhesives
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G01N33/521Single-layer analytical elements
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Dermatology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Materials Engineering (AREA)
  • Medicinal Preparation (AREA)
  • Adhesives Or Adhesive Processes (AREA)
  • Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
  • Peptides Or Proteins (AREA)
  • Fats And Perfumes (AREA)
  • Refuse Collection And Transfer (AREA)
  • Containers And Plastic Fillers For Packaging (AREA)
  • Extrusion Moulding Of Plastics Or The Like (AREA)
  • Coating Apparatus (AREA)
  • Wrappers (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Materials For Medical Uses (AREA)

Abstract

phe invention concerns a device for the release of substances made of hot-melt adhesives, with uniform or non-uniform distribution of the substances. The hot-melt adhesive has a processing temperature between 40 and 80 degrees Celsius, preferably between 40 and 60 degrees Celsius, and ideally between 40 and 55 degrees Celsius. Also described is a process for manufacturing the device in which the melted hot melt-adhesive containing the substances to be released is applied continuously or intermittently to a support at a hot-melt adhesive temperature between 40 and 80 degrees Celsius, preferably 40 and 60 degrees Celsius, and ideally 45 and 55 degrees Celsius, and in which, if necessary, a protective coating material is applied.

Description

1UItLA (51) (43) AjJ--225U688 JWTENJ PC~I ~WELTORGANISATION FOR GEISTIGES EIGENTUM PAW dA Internationales INTERNATIONALE ANMELDUNG VEROFFENTLICHT NACH DEM VERTRAG OBER DIE INTERNATIONALE ZUSAMMENARBEIT AUF DEM GESIET DES PATENTWESENS (PCT) (51) Internationale Patentklassifikation 4 (11) Internationale Veriiffentlichungsnummer: WO089/ 01787 A61L 15/03, GOIN 33/48 Al (43) Internationales Verbffentlichungsdatum: 9. NMlrz 1989 (09.03,89) (21) Internationales Aktenzcichen: PCT/DE88/00477 (74) Anwalt: NEIDL-ST!'?PLER, Cornelia; Rauchstrage 2, (22) Internationales Annieldedatum: D80 irce 1 D) 3. August 1988 (03.08.88) (81) Bestimmungsstaaten: AU, DK, Fl, HU, JP, KR, NO,
US.
(31) Prior-tl4tsakctenizeichen: P 37 29 165.3 P 37 43 945.6 Veriiffentlicht (32) Prioritlitsdaten: 1. September 1987 (0 1.09.87) Mit internationalem Recherchenbericht.
23. Dezember 1987 (23,12.87) (33) Pnroritfitsiand: DE (71) Anmelder (fiir alle Bestimmungsstaatien ausser LTS LOMANTHRPI-YSEM MB63C.683~ KG [DE/DE]; Irlicher StraBe 55, D-5450 Neuwied 12
(DE).
(72) Erfinder;und X1A.JJP- 11 -AY 19 Wrind erfAnmelder (nur fir US) JAEGER, Halvor [DE/DE] Brilhlweg 9-1 1, D-7910 Neu-Ulm ASRLA HOFFMANN, Hans-Rainer [DE/DE]* Burghofstrage ASRLA 123, D-5450 Neuwied 22 MECONI, Reinhold 31MR18 [DE/DE]; Alemannenstrage 42, D-5450 Neuwied 11 31MR18 KLEIN, Robert-Peter [DE/DE]; Winkingerstraae 3, D-5450 Neuwvied 11I PATENT OFC (54) Title: DEVICE FOR RELEASE OF SUBSTANCES, PROCESS FOR ITS MANUFACTURE AND USE THERE-
OF
(54) Bezelchnung: VORRICHTUNG ZUR ABGABE VON STOFFEN, VERFAHREN ZU IHRER HERSTELLUNG, SOWIE IHRE VERWENDUNG (57) Abstract The Inmencion conicerns a device for the release of substances made if hot-melt adhesives, with uniform or non-uniform distribution of the substances. The hot-melt adhesive has a processing temperature between 40 and 83 degrees Celsius, preferably between 40 and 60 degrees Celsius, and ideally between 40 and 55 degrees Celsius. Also described is a process for manufacturing the device in which the melted hot melt-adhesive containing the substances to be released -applied continuously or intermittently to a support at a hot-melt adhesive temperaliure between 40 and 80 degrees Celsius, preferably 40 and 60 degrees Celsius, and ideally 45 and 55 degrees Celsius, ane, in which, if necessary, a protective coating material is applied.
(57) Zusammenfassung Die Erfindung betrifft eine Vorrichtung zur Abgabe von Stoffen aus Haftschmelzklebern mit ungleichmaliiger oder gleichmllBiger Verteilung der Stoffe, bei der der Haftschmelzkleber eine Verarbeitungstemperatur zwischen 40 und Grad Celsius, bmvrzugt zwischen 40 und 60 Grad Celsius und besonders bevorzugt zwischen 40 und 55 Grad Celsius hat sowe ein Verfahiren zu ihirer Herstellung tinter ILontinuierlichem oder diskontinuierlichem Aufbringen abzugebenden Stoff enthaltenden geschmolzenen Haftschmelzklebers bei einer Temperatur des Haftschmelzklebers zwischen 40 und 80 Grad Celsius, bevorzugt 40 bis 60 Grad Celsius und besonders bevorzugt 45 bis 55 Grad Celsius auf einen Tralger und ggt. Anbringen des Schutzschichtmaterials.
-1- The invention relates to an apparatus for the release of substances from contact adhesives, with a non-uniform or irregular distribution of the substances, process for the preparation thereof and the use thereof.
Typical representatives of such apparatuses are active substance-containing plasters, indicator systems, perfume-releasing apparatuses and the like, where they are frequently more particularly used in the medical field for the controlled or uncontrolled release of substances. Particular significance hL- been attached to the controlled apparatuses in the form of transdermally controlled systems. It is already known in connection therewith to apply an active substance-containing layer from the melt. EP-OS 0177893 discloses a non-adhesive cellulose eter gel which can be applied from the melt and in which active substances can be distributed. This gel is hot processed and is non-adhesive. DE-OS 32 22 800 discloses a transdermal system, in which active substance packed in microcapsules is present in a thermally shapeable, adhesive matrix material, which is applied from the melt.
For temperature-sensitive active substances with a low melting point or which can be easily decomposed, attempts have also been made to produce non-adhesive active substance-containing matrixes at ambient temperature. For example, it is stated in US Patent 4 379 454 (Can.pbell et al.) that an active substance solution brought to a dersired viscosity value by means of gelling agents at ambient temperature can be used for the 20 active substance layer. It is known from US Patent 4 559 222 (Enscore et al.) to use a mixture of mineral oil/polyisobutylene and colloidal silicon dioxide prepared at ambient temperature as a viscous active substance layer for oil-soluble active substances, whereby said layers can also be made in contact adhesive manner, DE-OS 32 33 800 (ALZA) describes an active substance layer from an active substance solution thickened by means 25 of a rheological agent, such a cellulose, a polysaccharide fte **f f: f9 *JVT 0 -2or a silicon compound, which is nonadhesive and is also suitable for rapid active substance release.
US Patent 3 923 939 discloses shaping active substances, such as tetracycline, in an ethylene-vinyl acetate copolymer layer by melt pressing.
In EP-OS 86 468 an oral antidiabetes sulphonyl urea derivative in a nonadhesive hot melt mass with a melting point of 30 to 900C is filled into capsules in predetermined doses from the melt. US Patent 3 957 966 discloses that active substances can be processed in nonadhesive hot melt masses.
It is known from DE-OS 30 07 363 'o use a contact adhesive mixture of a thermoplastic elastomer, preferably a block polymer of general formula A-B-A, a tackifying resin with oil or higher fatty acids and active substance for producing a simple transdermal system. The contact adhesive mixture described therein is only suitable for relatively temperatureresistant active substances, which are able to withstand temperatures of 1200C and higher. US Patent 3 699 963 discloses mixing oxytocin with contact adhesive for producing a transdermal therapeutic system and shaping thereof at a temperature above 900C. The thus produced transdermal systems are inexpensive to produce and ensure a constant active substance transfer via the whole-area adhesion of the system to the skin.
The prior art processes for producing such systems are not suitable for transdermal systems containing temperature-sensitive substances, such as scopolamine. Therefore hitherto contact adhesive active substance layers with temperature sensitive active substances have preferably been formed from the solution and the solvent evaporated.
The use of solvents in the preparation of active substance-containing adhesive layers is disadvantageous for several reasons. The preparation of the solutions requires at least one additional, complicated process stage. It leads to high technical effort and expenditure in connection with the handling of the solvents, whilst in addition for medical urposes it is necessary to use extremely pure and therefore expensive solvents, Z U V' -3in order to ensure a corresponding freedom from residue in the apparatus for the dissolving of the adhesive or its starting materials. Another problem is to achieve freedom from solvent in the apparatus, for which purpose it is necessary to use expensive drying sections and suction installations. Costs are additionally incurred through the recovery or separation of the solvent, in order to avoid pollution of the environment. An additional risk is caused by the flammability of most solvents. In addition, most organic solvents are harmful to the human organism, so that complicated and costly protective measures must be taken for personnel working in the plant.
The problem of the present invention is therefore to avoid the aforementioned disadvantages of such apparatuses and processes according to the prior art.
The invention provides a device for the release of substances from pressure sensitive adhesives having a non-uniform or uniform distribution of the substances in the pressure sensitive adhesives, characterized in that a mixture of pressure sensitive ad :isive and substance or a solution of the substance in the pressure sensitive adhesive is present, the pressure sensitive adhesive having a processing temperature of between 40 0 C and 80 0
C.
The present invention makes it possible to work without solvents at low temperatures, so that there is considerable saving on materials, a speedier production of the apparatus without the time consuming drying stages, as well as a production of the inventive apparatuses which leads to less pollution of the environment, which inter alia leads to a 20 considerably less expensive and also solvent-free product.
When using highly volatile and/or thermally unstable substances to be released, the following measures are generally appropriate for processing purposes: A. working at very low temperatures, B. increasing the external pressure in order to reduce evaporation, 25 C. saturation of the vapour chamber over the melt with the vaporous substance and D. working with a minimum volatile substnce quantity in the melt.
irne *I r ccf> -4- Obviously these measures, such as for example working in an encapsulated plant, are limited by the rules known to the Expert through the intended use of the apparatus to be produced and also the material circumstances.
The inventive apparatuses, particularly transdermal systems can for example be used for local or systemic, transdermal active substance administration in human or veterinary medicine or cosmetics and are preferably used for the release of temperature-sensitive and/or highly volatile substances.
Contact adhesive or the alternative term 'pressure sensitive adhesive' is here understood to mean any contact adhesive, which is adequately liquid when hot to permit problem free application at a temperature above approximately As inventively usable contact adhesives can inter alia be used those which are know to the Expert and such as are inter alia described in DE-OS 15 94 268 (SUN OIL DE-OS 24 13 979 DU PONT DE NEMOURS), DE-OS 24 35 863 (DYNAMIT NOBEL AG), DE-OS 28 00 302 (CIBA GEIGY), EP-A-104 005 (PERSONAL PRODUCTS JP 6104 2583 and JP 61 281 819, EP-OS 131 460 (EXXON), EP-OS 234 856 (EXXON), EP-OS 185 992 t o 4 e i* ft ft ft9tt eZ I MtWl f 5 (EASTMAN KODAK), as well as US Patents 36 99 963 and 4 358 557 (EASTMAN KODAK) and express reference is made to this prior art to avoid unnecessary repetition.
The basic polymers can be constituted e.g. by polyamides, polyesters, polycaprolactams, polycaprolactone, ethylene-vinyl acetate copolymers (EVA), ethylene-ethylacrylate copolymers (EEA), polyvinylethers, polyacrylate esters, polyvinylacetals, polyviny.acetates, styrene-butadiene block polymers, isoprene block polymers, polyurethanes, ethylcellulose, cellulose acetate-butyrate, synthetic rubbers neoprene rubber), polyisobutylene, butyl rubber, acrylonitrile-butadiene copolymers, epoxy resins, melamine resins, phenol-formaldehyde resins and resorcinol-formaldehyde resins and inter alia the following modifying resins can be used: hydrogenated colophony, polymerized colophony, dimerized resin acids, disproportionated colophony, colophony methyl esters, hydrogenated colophony glycerol esters, hydrogenated colophony methyl esters, pentalesters, hydrogenated colophony triethyleneglycolesters, hydroabiethyl alcohol and its derivatives, glycerol estersditriolesters and pentaesters of resin acids, polymerized colophony pentalesters, dimerized colophony pentalesters, dimerized colophony glycerol esters, esters of maleic acid or phenol-modified colophony, aromatic and aliphatic hydrocarbon resins, hydrogenated resins, polyterpene resins, modified terpene resins, waxes, low molecular weight polyethylene and polypropylene and alkyl-styrene copolymers. To these resins can optionally be added plasticizers, such as e.g. adipic acid esters, phosphoric acid esters, phthalic acid esters, polyesters, fatty acid esters, citric acid esters or epoxide plasticizers.
It is also possible to admix stabilizers, such as tocopherol, substituted phenols, hydroquinones, pyrocatechols, aromatic amines and optionally also fillers, such as e.g. titanium dioxide, magnesium oxide, zinc oxide and silicon dioxide.
The formation of components of the apparatus having bor-met-contact adhesive with a processing temperature between 40 and 80 0 C can take place by extrusion, pouring, roller application, knife coating, spraying or printing processes.
(i -6- A limit value for the processability of the hot4-mel- contact adhesive in many of these processes is at a viscosity of approximately 80,000 Pa.
If the substrate to be treated with the adhesive, a component of the apparatus, could be damaged by the temperature of the hot-applied adhesive, either by decomposition, reaction or partial melting, it is possible to use a cooled substrate. Cooling can take place by per se known processes, such as the introduction of cold inert gases or contacting With a cooling surface.
The hoe-mea contact adhesive can e.g. be applied in layer form or in individual areas in accordance with a predetermined pattern to the protective layer or the covering material.
As a function of the intended use and e.g. if the substance to be released is to be released through the backing layer, such as ca be '!ha &asse with essential oils, such as fragrances, the -hc-mel contact adhesive can be finished with a carrier permeable with respect to the substance or substances to be released, whilst in the embodiment of the apparatus as a transdermal system, where the substance is only to be delivered to the skin, preference is given to a backing layer which is impermeable for the substance to be delivered.
The inventive process makes it possible to obviate the use of solventcontaining, contact adhesive materials in the processing of temperaturesensitive, highly volatile substances, which considerably increases the safety of production, because it is now certain that no toxic solvent residues can remain in the medicinal administration form, as well as bringing about a greatly simplified application process and considerable production cost savings. The process can naturally also be used in advantageous manner for less temperature-sensitive substances, because this also leads to considerable cost savings.
The expression "substances" in connection with the present invention is understood to mean ch(mical elements, organic and inorganic compounds, -7 which can migrate out of the componeqts containing them in such an apparatus and can thereby bring about a sought effect. Among the uses of the inventive apparatus particular significance is attached to human and veterinary medicine, a realization of the invention in plaster form being particularly preferred.
Typical substances which can be administered by means of inventively produced apparatuses are: aceclidine, amjphetaminil, amphetamine, amylnitrite, apophedrin, atebrin, alprostadil, a.u:lene, arecoline, anethole, amylenehydrate, acetylcholine, acridine, adeiiosintriphosphoric acid, L-malic acid, alimemazine, allithianine, allyl isothiocyanate, aminoethanol, apyzine, apiol, azatadine, aiprenolol, ethinazone, benzoylperoxide, benzyl alcohol, bisabolol, bisnorephedrihe, butacetoluid, benactyzine, campher, colecalciferol, chloralhycdra tg, clemastine, chlorobutanol, capsaicin, cyclopentamine, clobutinol, chainazulene, dimethocaine, codeine, chloropromazine, quinine, chiorothyrnol, cyclophosphamide, cinchocaine, chlorambucil, chlorphenesin, diethylethane, divinylethane, dexchlorpheniramine, dinoprostone, dixyrazine, ephedrine, ethosuxitnide, enallylpi-opymal, emylcamate, erytroltetranitrate, emetine, enflurane, eucalyptol, etofenamate, ethylmorphine, fentanyl, fluanisone, guajazulene, halothane, hyoscyamine, histamine, fencarbamide, hydroxycaine, hexylresorcinol, isoaminilcitrate, :sosorbidedinitrate, ibuprofen, iodine, iodoform, isoaminile, lidocaine, lopirine, levamisole, methadone, methyprylone, methy lpheni date, mephenesine, methylephedrine, reclastine, methopromazine, mesuximide, nicethamide, norpseudoephedrine, mentholt nethoxyflurane, methylpentinol, metixen, misoprostol, oxytetracaine, oxyprenolo oxyphenbutazone, oxyquInoline, pinene, prolintane, procycidine, piperazine, pivazide, phansuximide, procaine, phenindamine, promethazine, pentetrazole, profenaxnine, perazine, Phenol, pethidine, pilocarpine, prenylamine, phenoxybenzamine, resochin, scopolamine, salicyclic acid ester, sparteine, trichiorcethylene, timolol, trifluperazine, tetracaine, trinipramine, tranylcypromine, trimethadione, tybamate, thymol, thioridazine, valproic acid, verapamil, as well as other active substances which can be taken' up through the skin. obviously this lii.t is not conclusive.
-8- Typical compositions for hot walt contact adhesives to be used are those prepared from between 10 and 100% by weight, preferably 20 to 80% by weight and in particularly preferred manner 20 to 50% Ly weight of polymer, between 10 and 80% by weight, preferably 15 to 60% by weight of plasticizer, between 10 and 80% by weight, preferably 15 to 60% by weight of tackifier, optionally 0.1 to 5% by weight of antiagers and optionally 0 to 70% by weight of fillers, the sum of the percentages of the components always being 100.
Preferably the hot me! contact adhesive contains 10 to 50% by weight of styrene-isoprene-styrene synthetic rubter, such as is commercially available under the name CARIFLEX TR 1107 of SHELL, between 10 and by weight of a hydrogenated alcohol, such as is commercially available under the name ABITOL from HERCULES, between 10 and 80% by weight of a hydrocarbon resin, e.g. HERCURES C from HERCULES, between 1 and by weight of esters of venetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL and optionally up to 5% by weight of antiagers, such as hydroquinone etc. as well as up to 70% by weight of fillers.
In a further preferred embodiment of the invention the ho mlt contact adhesive has 10 to 50% by weight of a polycaprolactone, e.g. CAPA 650 of INTEROX, between 10 and 80% by weight of a hydrogenated alcohol, e.g.
ABITOL of HERCULES, between 10 and 80% by weight of a hydrocarbon resin, e.g. HERCURES C of HERCULES, between I and 40% by weight of esters of vegetable fatty acids, such as MIGLYOL 812 of DYNAMIT NOBEL and optionally up to 5% by weight of antiagers, as well as up to 70% by weight of fillers.
It c'n be advantageous for the t.-melt. contact adhesive to have 10 to by weight of polyethylene-vinyl acetate, such as EVATANE 28-25 of ATOCHEM, between 10 and 80% by weight of a hydrogenated alcohol, e.g.
ABITOL of HERCULES, between 10 and 80% by weight of a hydrocarbon rerin, e.g. HERCURES C of HERCULES, between 1 and 40% by weight of esters of vegetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL and optionally up to 5% by weight of antiagers, such as hydroquinone, etc. and up to by weight of fillers.
-9- A suitable hot elt contact adhesive can contain up to 10 to 50% by weight of polyurethane, such as e.g. LUPHEN P 1110 of BASF, between 10 and by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES, between and 80% by weight of a hydrocarbon resin, e.g. HERCURES C of HERCULES, between I and 40% by weight of esters of vegetable fatty acids, e.g.
MIGLYOL 812 of DYNAMIT NOBEL and optionally up to 5% by weight of antiagers, as well as up to 70% by weight of fillers.
It is also possible for the 4Ke-B4_- contact adhesive to contain up to to 50% by weight of polyamide, such as e.g, EURELON 930 of SCHERING, between 10 and 80% by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES, between 10 and 80% by weight of a hydrocarbon resin, e.g.
HERCURES C of HERCULES, between 1 and 40% by weight of esters of vegetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL and optionally up to by weight of antiagers, as well as up to 70% by weight of fillers.
It is also possible to use a 4t-ma4t- contact adhesive with 10 to by weight oC epoxide, e.g. EUREPOX 7001 of SCHERING, between 10 and by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES, between and 80% by weight of a hydrocarbon resin, e.g. HERCURES C of HERCULES, between 1 and 40% by weight of esters of vegetable fatty acids, e.g.
MIGLYOL 812 of DYNAMIT NOBEL and optionally up to 5% by weight of antiagers, such as hydroquitone, etc., as well as up to 70% by weight of fillers.
Another h -malt.contact adhesive usable in the production of inventive t-ansdermal systems has up to 10 to 50% by weight of polyisobutene with a tacky, rubber-like consistency, such as e.g. OPPANOL B 50 of BASF, between 10 and 80% by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES, between 10 and 80% by weight of a hydrocarbon resin, e.g.
HERCURES C of HERCULES,, between 1 and 40% by weight of esters of vegetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL and optionally up to 5% by weight of antiagers, as well as up to 70% by weight of fillers.
t is finally preerred to usect adhesives with a polyeste It is finally preferred to use he;-ml- contact adhesives with a polyester base and which e.g. contain between 10 and 80% by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES, between 10 and 80% by weight of a hydrocarbon resin, e.g. HERCUPRES C of HERCULES, between 1 and 40% by weight of esters of vegetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL and optionally up to 5% by weight of antiagers, as well as up to by weight of fillers.
Inventive apparatuses can also contain one or more substance depots, in which the substance is present in a higher concentration than the active substance-possessing-4h-t eeltcontact adhesive layer, so that higher substance doses can be processed and consequently the apparatus can remain in use longer before it has to be changed. Typical constructions appear e.g. in DE-OS 36 29 304. Preferred constructions of the invention are given in the subclaims, to which express reference is made.
Further features and advantages of the inventiol are explained in greater detail hereinafter relative to the drawings, wherein show: Fig. 1 a diagrammatically represented section through the layers of an inventive apparatus with a substance depot.
Fig. 2 a diagrammatically represented section through a further inventive apparatus with an active substance depot.
Fig. 3 a diagrammatically represented section through another embodiment of an inventive apparatus without a substance depot.
Fig. I shows an inventive apparatus, which is in this case in the form of a plaster-like, active substance-containing, transdermal, therapeutic system. It has a hoe-mfel-t contact adhesive layer 12, an active substance depot 14 in which the active substance has a higher concentration than in the het-mta44- contact adhesive layer 12, as well as an active substanceimpermeable carrier 10, on which rests the active substance depot 14 and which is stuck to the skin 18. Active substance now continuously migrates at a predetermined rate through the skin 18, so that the active 11 substance content of layer 12 decreases. The active substance decrease is compensated by an after-flow of active substance from the active substance depot 14, so that over a predeterminable period of time there is an equilibrium concentration of the active substance in the hot melt contact adhesive layer 12, which ensures the delivery of a constant active substance quantity to the skin 18.
Fig. 2 shows another embodiment of an inventive apparatus, in which an active substance depot 14 is surrounded on all sides by the Lot-.-~ contact adhesive layer 12. This embodim~ent is particularly suitable if a large contact surface between th active substance depot and the hn-wl contact adhesive layer is desired for a rapid active substanc~e delivery to the 44t-a contact adhesive layer.
Fig. 3 shows a further simple embodiment of an inventive apparatus, in which an active substance-containing h-w%44 contact adhesive layer 12 is applied to an impermeable carrier mafter~al 10 in such a way that the latter covers the layer 12 on three sides. With the free 1i.oa3.t contact adhesive surface it is stuck to the skin 18, so that a wholearea contact is ensured over the application time and the transfer of the active substance to the skin always takes pl(ce over a constant surface and at a constant speed.
The inventively improved pro~duction of an inventive apparatus will now described. Firstly the mixt-are of the co~ponents of the o ml contact adhesive and the substance, to be administered is prepared. This mixture is then brought to the processing temperature and then applied from the melt to a carrier material. The further processing, such as the application of an abhesively finished protective layer material take place in the conventional way.
T~~O

Claims (1)

12- THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: 1. A device for the release of substances from pressure sensitive adhesives having a non-uniform or uniform distribution of the substances in the pressure sensitive adhesives, characterized in that a mixture of pressure sensitive adhesive and substance or a solution of the substance in the pressure sensitive adhesive 's present, the pressure sensitive adhesive having a processing temperature of between 40 0 C and 80 0 C. 2. A device according to claim 1, characterized in that said processing temperature is between 40°C and 60 0 C. 3. A device according to claim 1, characterized in that said processing temperature is between 40'C and 4. A device according to any preceding claim, characterized in that the pressure sensitive adhesive, having the substance(s) to be released, is present as one or more layers. A device according to any one of claims 1 to 4, characterized in that the pressure sensitive adhesive is provided with a carrier, which is permeable or impermeable to the substance(s) to be released. 6. A device according to any one of the preceding claims, characterized in that the pressure sensitive adhesive is produced on the basis of styrene-isoprene-styrene blot' Spolymers,polycaprolactones, ethylene-vinylacetatecopolymers,polyurethane,polyepoxides, i. *polyisobutene, polyvinylethers, optionally with the addition of plasticizers, tackifiers, filler materials, anti-agers, and/or thixotropic agents. 7, A device according to claim 6, characterized in that the pressure sensitive adhesive i' is produced from between 10% by weight and 80% b' weight, preferably 20% by weight to 80% by weight and especially preferably 20% by weight to 50% by weight polymer, btween 1% by weight and 80% by weight preferably 1% by weight to 60% by weight plasticizer, between 10% by weight and 80% by weight, preferab!, 15% by weight to 60% by weight tackifier, optionally 0.1% by weight to 5% by weight anti-agers and i l l 13 optionally 0% by weight to 70% by weight filler materials, the sum of the percentages of the components always being 100. 8. A device according to any one of the preceding claims, characterized in that it has a removable protective layer. 9. A method of producing a device according to one of the preceding claims, characterized by continuously or discontinuously applying a molten mixture of pressure sensitive adhesive and substance to be released at a temperature of the mixture of between and 80 0 C, preferably between 40 0 C to 60 0 C and especially preferably 45°C to 55 0 C, to a carrier and optionally applying a protective layer material. 10. A device for the release of substances from pressure sensitive adhesives, substantially as herein described with reference to the accompanying drawings. DATED this 3 March 1993 CARTER S ,TH BEADLE Fellows Institute of Patent Attorneys of Australia Patent Attorneys for the Applicant: LTS LOHMANN iTHERAPIE-SYSTEME GMBH CO KG i t i* 4 8 ft 4 f 3ikm
AU22506/88A 1987-09-01 1988-08-03 Device for release of substances, process for its manufacture and use thereof Ceased AU636835B2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE3729165 1987-09-01
DE3729165 1987-09-01
DE19873743945 DE3743945A1 (en) 1987-09-01 1987-12-23 DEVICE FOR DELIVERING SUBSTANCES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE
DE3743945 1987-12-23

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AU2250688A AU2250688A (en) 1989-03-31
AU636835B2 true AU636835B2 (en) 1993-05-13

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JP (1) JP2781579B2 (en)
KR (1) KR970006448B1 (en)
AT (1) ATE83655T1 (en)
AU (1) AU636835B2 (en)
CA (1) CA1333688C (en)
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DE (2) DE3743945A1 (en)
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ES (1) ES2036242T3 (en)
FI (1) FI96577C (en)
GR (1) GR3006666T3 (en)
HU (1) HU205268B (en)
IE (1) IE62943B1 (en)
IL (1) IL87538A (en)
MY (1) MY103757A (en)
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NZ (1) NZ225918A (en)
PL (1) PL163710B1 (en)
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DE4301781C2 (en) * 1993-01-23 1995-07-20 Lohmann Therapie Syst Lts Patch containing nitroglycerin, process for its production and use
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US5380760A (en) * 1993-11-19 1995-01-10 Minnesota Mining And Manufacturing Company Transdermal prostaglandin composition
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DE19825499C2 (en) 1998-06-08 2003-07-17 Beiersdorf Ag Patches containing active ingredients
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DE10056009A1 (en) * 2000-11-11 2002-05-16 Beiersdorf Ag Well tolerated plaster for controlled delivery of hyperemic agents, having active agent-containing matrix comprising polyisobutylene, amorphous poly-alpha-olefin and filler
DE10118282A1 (en) 2001-04-12 2002-12-05 Lohmann Therapie Syst Lts Pressure sensitive adhesive based on ethylene-vinyl acetate copolymers and adhesive resins, for medical purposes
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EP0305756B1 (en) 1992-12-23
CZ587388A3 (en) 1993-10-13
HU884702D0 (en) 1990-04-28
NO178684C (en) 1996-05-15
PL163710B1 (en) 1994-04-29
EP0305756A1 (en) 1989-03-08
SK587388A3 (en) 1998-09-09
YU166288A (en) 1990-12-31
DK175442B1 (en) 2004-10-25
NO891507L (en) 1989-04-12
NO178684B (en) 1996-02-05
HUT53544A (en) 1990-11-28
DE3743945A1 (en) 1989-03-09
FI892053A0 (en) 1989-04-28
NO891507D0 (en) 1989-04-12
IE62943B1 (en) 1995-03-08
PT88378A (en) 1989-07-31
ATE83655T1 (en) 1993-01-15
WO1989001787A1 (en) 1989-03-09
DE3743945C2 (en) 1992-02-20
CA1333688C (en) 1994-12-27
HU205268B (en) 1992-04-28
MY103757A (en) 1993-09-30
DK210289A (en) 1989-04-28
SK279300B6 (en) 1998-09-09
JPH02500594A (en) 1990-03-01
PL274486A1 (en) 1989-05-02
KR970006448B1 (en) 1997-04-28
PT88378B (en) 1993-10-29
NZ225918A (en) 1990-03-27
FI96577B (en) 1996-04-15
CZ281743B6 (en) 1997-01-15
DK210289D0 (en) 1989-04-28
GR3006666T3 (en) 1993-06-30
FI892053A (en) 1989-04-28
IE882554L (en) 1989-03-01
KR890701143A (en) 1989-12-19
YU47201B (en) 1995-01-31
AU2250688A (en) 1989-03-31
JP2781579B2 (en) 1998-07-30
IL87538A (en) 1994-02-27
ES2036242T3 (en) 1993-05-16
IL87538A0 (en) 1989-01-31
DE3876898D1 (en) 1993-02-04
FI96577C (en) 1996-07-25

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